Unmasking tumor-induced osteomalacia: A diagnostic odyssey from ankylosing spondylitis to fibroblast growth factor 23-mediated hypophosphatemia

Abstract

Background: Tumor-induced osteomalacia is a rare paraneoplastic syndrome caused by autonomous secretion of fibroblast growth factor 23 (FGF23) by occult mesenchymal tumors. Its insidious presentation frequently mimics inflammatory arthropathies, leading to misdirected therapy and severe diagnostic delay. Case summary: A 29-year-old Bangladeshi housewife presented with a 3-year history of progressive generalized body pain and 3 months of severe bilateral groin pain causing a waddling gait without Cushingoid stigmata. She had previously received ineffective treatment for presumed ankylosing spondylitis. Examination revealed diffuse bony tenderness and restricted joint motion. Biochemical evaluation demonstrated normal calcium, intact parathyroid hormone, and vitamin D sufficiency but persistent hypophosphatemia (nadir 1.1 mg/dL) and markedly elevated alkaline phosphatase (993 U/L). Urinary studies showed renal phosphate wasting with a low tubular maximum phosphate reabsorption to glomerular filtration rate (0.88 mg/dL). Serum FGF23 was elevated at 301.50 pg/mL. Imaging revealed bilateral femoral subcapital neck insufficiency fractures and pseudofractures in the pelvis and fibulae, while 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) and a femoral neck biopsy showed no malignancy. Because 68Ga-DOTATATE PET/CT was unavailable, the tumor remained occult, and she was commenced on bridging medical therapy with oral phosphate, active vitamin D, calcium, and zoledronic acid. Conclusions: Unexplained chronic musculoskeletal pain with insufficiency fractures necessitates early serum phosphate testing when calcium panel is normal. Tumor-induced osteomalacia remains a clinical and biochemical diagnosis even when culprit tumors evade initial functional imaging. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S83]